Pan-amyloid oligomer specific scFv antibody attenuates memory deficits and brain amyloid burden in mice with Alzheimer's disease
| Autor: | Ran Zhang, Ya-nan Li, Min Zhao, Shao-wei Wang, Rui-tian Liu, Xiao-lin Yu, Wei-wei Zhou, Yu-jiong Wang, Ya-jing Su |
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| Rok vydání: | 2012 |
| Předmět: |
Genetically modified mouse
Amyloid BACE1-AS Amylin Mice Transgenic Plaque Amyloid Presenilin Amyloid beta-Protein Precursor Mice Alzheimer Disease Heat shock protein Cell Line Tumor medicine Presenilin-1 Animals Humans Heat-Shock Proteins Memory Disorders Amyloid beta-Peptides Chemistry Cell Membrane P3 peptide Brain medicine.disease Peptide Fragments Mice Inbred C57BL Neurology Immunology Cancer research Female Neurology (clinical) Alzheimer's disease Single-Chain Antibodies |
| Zdroj: | Current Alzheimer research. 11(1) |
| ISSN: | 1875-5828 |
| Popis: | Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naive human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ40/42, prion peptide 106-126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD. |
| Databáze: | OpenAIRE |
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